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Friday, July 24, 2009

Nobel Laureate: Peyton Rous


The Nobel Prize in Physiology or Medicine 1966

"for his discovery of tumour-inducing viruses"

Peyton Rous (1879 - 1970) won the Noble Prize in 1966 for his discovery and characterization of several viruses that cause cancer in birds and mammals. He is best known for his work on Rous Sarcom Virus (RSV), a retrovirus that infects chickens and causes cancer.

The original work was done many years earlier as he describes in his Nobel lecture.
In 1910 I described a malignant chicken sarcoma which could be propagated by transplanting its cells, these multiplying in their new hosts and forming new tumors of the same sort. In other ways the growth showed itself to be a neoplasm of a classical sort, yet, as reported in 1911, its cells yielded a causative virus. Numerous workers had already tried by then to get extraneous causes from transplanted mouse and rat tumors but the transferred cells had held their secret close. Hence the findings with the sarcoma were met with down-right disbelief, though soon several other, morphologically different, "spontaneous" chicken tumors were propagated by transplantation and from each a virus was got causing growths of its kind. Not until after some 15 years of disputation amongst oncologists were the findings with chickens deemed valid, and then they were relegated to a category distinct from that of mammals because from them no viruses could be obtained. Only in 1925, through the efforts of a British worker, W.E. Gye, was much attention given them by scientists.

The virus causing the chicken sarcoma first studied, now generally termed the RSV, has been maintained for more than fifty-five years and is still studied in many countries. Throughout most of this time it would engender growths only in chickens and closely related fowls; but of late several extraneous, non-neoplastic viruses have become associated with it, during its passage in unusual avian hosts; and its scope has thus been so enlarged that now not at few mammals, including monkeys, have been found to develop tumors after inoculation with the enhanced material
For many years the idea that a virus could cause cancer was not part of mainstream oncology. It took a number of other advances to make the idea acceptable. Part of the problem was due to a lack of understanding about the various modes of viral infection. Work on bacterial viruses (bacteriophage) showed clearly that a virus genome could integrate into the normal cellular chromosome and be carried along in all the offspring of those cells.

Fifty years after the initial discovery of a cancer-causing virus, scientists could finally begin to formulate a mechanism based on the results of the phage ground and bacterial geneticists. It's interesting to see the state of knowledge in 1966 as seen in the presentation speech.
Nobel Laureates
The situation changed radically in the 1950's. The study of tumour viruses is a central area of modern cancer research. Two developments are responsible for this remarkable change. Recent developments in microbial genetics have lead to reinterpretation of the virus concept itself. It turns out that certain types of virus can introduce parts of their own genetic material into a cell without killing it or inhibiting its multiplication. The virus material thus introduced may become actually integrated with the gene material of the recipient cell and behave as a new hereditary factor. Virus infection can thus lead to a permanent change in some cellular characteristics. This re-evaluation of the virus concept made it possible to understand how a tumour virus might change the regulated behaviour of normal cells to the malignant proliferation characteristic of cancer cells. In the same period many new viruses capable of inducing malignant tumours in mammals were discovered. In 1981 Gross found a virus that induces leukemia in mice. A few years later he and two women scientists, Stewart and Eddy, isolated a remarkable new virus, called polyoma, capable of inducing an array of tumours in many different mammalian species. Since 1960 more than a dozen new tumour virus types have been isolated. It was established, furthermore, that tumour viruses could change normal to cancer cells in the test tube after a very short time of contact. This opened the way for direct studies on cancerous transformation of human cells, an approach previously hidden behind the walls of the living organism. Remarkably enough, it could be shown that Rous' own virus, previously regarded as lacking any importance for mammals, induces cancer under certain conditions in many different mammalian species and may even transform human cells in test tube cultures. Swedish scientists in Lund and Uppsala have made important contributions in this regard. It is not yet clear in which way viruses induce cancer but there is much to indicate that the virus does not behave like a little boy setting fire to a hayrick and running away; part of the viruses' own genetic material seems to be directly responsible for the malignant behaviour of the virus transformed tumour cell.

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